Transport across the Cell Membrane PDF

3 Transport across the cell membrane ILOs By the end of this lecture, students will be able to 1. Demonstrate the different transport mechanisms across the cell membrane 2. Compare movement through channels to movement by simple or facilitated diffusion 3. Differentiate between...

3 Transport across the cell membrane ILOs By the end of this lecture, students will be able to 1. Demonstrate the different transport mechanisms across the cell membrane 2. Compare movement through channels to movement by simple or facilitated diffusion 3. Differentiate between primary and secondary active transport Substances generally move across cellular membranes via transport processes that can be classified as passive or active, depending on whether they require cellular energy. In passive process, a substance moves across the cell membrane along any type of gradient without expenditure of energy. On the other hand, in active transport, the transport of substances takes place against any type of gradient by the utilization of energy. Passive transport The transport of the substances along the concentration or electrochemical gradient or both is called passive transport or diffusion. The substances are transported from region of higher concentration to a lower concentration. This type of transport doesn’t require energy but it may needs the help of carrier proteins of the cell membrane. 1)-Simple Diffusion Simple diffusion is a passive process in which substances move freely through the lipid bilayer of the plasma membranes of cells without the help of membrane transport proteins. The lipid layer is only permeable to lipid- soluble substances such as oxygen, carbon dioxide, and nitrogen gases; fatty acids; steroids; and fat-soluble vitamins (A, D, E, and K). Small, uncharged polar molecules such as water, urea, and small alcohols also pass through the lipid bilayer by simple diffusion. 2)-Facilitated Diffusion a)-Channel-mediated facilitated diffusion: A solute moves down its concentration gradient across the lipid bilayer through a membrane channel. Most membrane channels are ion channels, integral transmembrane proteins that allow passage of small, inorganic ions. Water soluble substances can diffuse through protein channels. The characteristic feature of these protein channels is the selective permeability. That is, each channel can permit only one type of ion to pass through it such as sodium channels, potassium channels, etc… Diffusion of ions through channels is generally slower than free diffusion through the lipid bilayer because channels occupy a smaller fraction of the membrane’s total surface area than lipids. Some of protein channels are continuously opened (leak channels) and most of channels are always closed (gated channels). The gated channels are opened only when required and it is of 2 types: Page 1 of 4  Voltage gated channels: these channels open when there is a change in the electrical potential. Ligand gated channels: are opened by binding to a ligand as some hormonal substances. b)-Carrier-mediated facilitated diffusion: The water soluble substances having larger molecules cannot diffuse through the protein channels. They diffuse through cell membrane with the help of carrier proteins (transporters). These transporters are proteins that are part of the cell membrane. In carrier-mediated facilitated diffusion, a carrier moves a solute down its concentration gradient across the plasma membrane. The solute binds to a specific carrier on one side of the membrane and is released on the other side. Binding of the solute with the carrier leads to changes in the shape of the carrier. This physical change propels the solute into the interior of the cell. Substances that move across the plasma membrane by carrier mediated facilitated diffusion include glucose, fructose, galactose, amino acids and some vitamins. Figure 1: The difference between simple and facilitated diffusion. 3)-Osmosis Osmosis is a type of diffusion in which there is net movement of water or any other solvent through a semipermeable membrane. Osmosis occurs only when a membrane is permeable to water but is not permeable to certain solutes. Like the other types of diffusion, osmosis is a passive process. In living systems, the solvent is water, which moves by osmosis across plasma membranes from an area of higher water concentration to an area of lower water concentration. Another way to understand this idea is to consider the solute concentration: In osmosis, water moves through a selectively permeable membrane from an area of lower solute concentration to an area of higher solute concentration. During osmosis, water molecules pass through a plasma membrane in two ways: (1) by moving between neighboring phospholipid molecules in the lipid bilayer via simple Page 2 of 4 diffusion, and (2) by moving through aquaporins, integral membrane proteins that function as water channels. Active transport It is the movement of substances against the chemical or electrical or electrochemical gradient. Active transport requires energy and a carrier protein. Active transport is considered an active process because energy is required for carrier proteins to move solutes across the membrane against a concentration gradient. Two sources of cellular energy can be used to drive active transport: (1) Energy obtained from hydrolysis of adenosine triphosphate (ATP) is the source in primary active transport; (2) energy stored in an ionic concentration gradient is the source in secondary active transport. Figure 2: The difference between passive and active transport 1)-Primary Active Transport This is the type of active transport in which the energy is liberated directly from hydrolysis of ATP. The carrier protein has ATPase activity which causes breakdown of ATP. The energy derived from hydrolysis of ATP changes the shape of a carrier protein, which “pumps” a substance across a plasma membrane against its concentration gradient. Indeed, carrier proteins that mediate primary active transport are often called pumps. The most prevalent primary active transport mechanism expels sodium ions (Na") from cells and brings potassium ions (K") in. Because of the specific ions it moves, Page 3 of 4 this carrier is called the sodium–potassium pump. Because a part of the sodium-potassium pump acts as an ATPase, an enzyme that hydrolyzes ATP, another name for this pump is Na!–K! ATPase. All cells have thousands of sodium–potassium pumps in their plasma membranes. 2)-Secondary Active Transport This is the type of active transport in which the substance moves against its electrochemical gradient. However the energy supplied for this transport doesn’t come directly from ATP, but it comes from the movement of another substance along its electrochemical gradient. When Na+ is transported by a carrier protein passively, another substance is also transported by the same protein simultaneously, either in the same direction of Na+ movement (co-transport) or in the opposite direction (counter- transport). The energy stored in a Na+ concentration gradient is used to drive other substances across the membrane against their own concentration gradients such as glucose and amino acids. A carrier protein (transporter) simultaneously binds to Na" and another substance and then changes its shape so that both substances cross the membrane at the same time. Types of carrier: Symporters: the carriers move two substances in the same direction at the same time as Na+ and glucose. Antiporters: the carriers move two substances in opposite directions across the membrane at the same time as Na+ and H+ in renal epithelial cells. Figure 3: Types of active transport Page 4 of 4  4 Cellular Homeostasis-Homeostatic control system ILOs By the end of this lecture, students will be able to 1. Relate Feedback /response loop to body homeostasis 2. Differentiate between +ve and –ve feedback mechanisms 3. Apply the process of -ve feedback loop on some homeostatic regulatory mechanisms as blood glucose level& body temperature 4. Correlate the distribution of body water and electrolytes among different compartments to the health and disease 5. Detect the different factors involved in body homeostasis 6. Integrate functions of different body systems serving the body homeostasis 7. Distinguish between osmolarity , osmolality , osmotic pressure and tonicity 8. Analyze the effect of different solutions on cell membrane 9. Locate the different ions in both ECF and ICF compartments 10. Relate the cell permeability and transport mechanisms to the cell membrane potential Homeostasis Homeostasis means the maintenance of constant internal environment. Control of Homeostasis Homeostasis in the human body is continually being disturbed. Some disruptions come from the external environment in the form of physical insults such as the intense heat day or a lack of enough oxygen. Other disruptions originate in the internal environment, such as change of blood glucose level. Fortunately, the body has many regulating systems that can usually bring the internal environment back into balance. Most often, the nervous system and the endocrine system, working together or independently, provide the needed corrective measures. Both means of regulation, however, work toward the same end, usually through negative feedback systems. Feedback Systems The body can regulate its internal environment through many feedback systems. A feedback system or feedback loop is a cycle of events in which the status of a body condition is monitored, evaluated, changed, re-monitored, reevaluated, and so on. Each monitored variable, such as body temperature, blood pressure, or blood glucose level, is termed a controlled condition. Any disruption that changes a controlled condition is called a stimulus. A feedback system includes three basic components: a receptor, a control center, and an effector (figure 1). 1. A receptor is a body structure that monitors changes in a controlled condition and sends input (nerve impulse or chemical signals) to a control center. This pathway is called an afferent pathway. 2. A control center in the body, for example, the brain, sets the range of values within which a controlled condition should be maintained (set point), evaluates the input it receives from receptors, and generates output commands when they are needed. Output from the control center typically occurs as nerve impulses, or hormones or other chemical signals. This pathway is called an efferent pathway. Page 1 of 9  3. An effector is a body structure that receives output from the control center and produces a response or effect that changes the controlled condition. In a feedback system, the response of the system “feeds backward to change the controlled condition in some way, either negating it (negative feedback) or enhancing it (positive feedback). Negative Feedback Systems A negative feedback system reverses a change in a controlled condition. If the activity of a particular system is increases, the regulatory mechanism will immediately reduce the activity. For example, consider the regulation of blood pressure. If the blood pressure (controlled condition) rises due to Figure (1): The feedback loop of homeostasis any stimulus, the following sequence of events occurs. Baroreceptors (the receptors), pressure- sensitive nerve cells located in the walls of certain blood vessels, detect the higher pressure. The baroreceptors send nerve impulses (input) to the brain (control center), which interprets the impulses and responds by sending nerve impulses (output) to the heart and blood vessels (the effectors). Heart rate decreases and blood vessels dilate (widen), which cause BP to decrease (response). This sequence of events quickly returns the controlled condition—blood pressure—to normal, and homeostasis is restored. Notice that the activity of the effector causes BP to drop, a result that negates the original stimulus (an increase in BP). This is why it is called a negative feedback system. Page 2 of 9 Example of negative feedback mechanism: Regulation of body temperature: Body temperature is regulated by negative feedback system (figure 2). The stimulus is when the body temperature exceeds or decreases below 37°C (set point). The receptors are the nerve cells with endings in the skin and brain, the control center is the temperature regulatory center in the brain, and the effector is the sweat glands and blood vessels throughout the body. If the body temperature rises above 37.0 ∘C, a negative feedback loop will act to bring it back down towards the set point. High temperature will be detected by receptors in the skin and brain. These receptors send signals to a temperature-regulatory control center in the hypothalamus. The control center checks our current temperature and compares it with the set point. Then it sends signals to the effectors (sweat glands and blood vessels). Blood vessels dilate with increase blood flow to skin which speed up heat loss into surroundings. Increase sweating will also help to decrease temperature through evaporation of sweat from skin. Heavy breathing can also increase heat loss. On the other hand, if body temperature decreases below its set point, low temperature will be detected by receptors in the skin and brain which send signals to the control center in the hypothalamus. This center sends signals to the effectors (sweat glands and blood vessels). Blood vessels constricts with decrease blood flow to skin which decrease heat loss into surroundings. Decrease sweating will also help to conserve body heat. The nervous system also sends signals to muscles to contract involuntarily (shivering) to generate heat. Figure (2) : Regulation of temperature by the negative feedback loop Page 3 of 9 Positive Feedback Systems Unlike a negative feedback system, a positive feedback system tends to strengthen or reinforce a change in one of the body’s-controlled conditions. The control center still provides commands to an effector, but this time the effector produces a physiological response that adds to or reinforces the initial change in the controlled condition. The action of a positive feedback system continues until it is interrupted by some mechanism. Normal childbirth (figure 3) and Suckling reflex provide good examples of positive feedback systems. These examples suggest some important differences between positive and negative feedback systems. Because a positive feedback system continually reinforces a change in a controlled condition, some event outside the system must shut it off. If the action of a positive feedback system is not stopped, it can “run-away” and may even produce life- threatening conditions in the body. The action of a negative feedback system, by contrast, slows and then stops as the controlled condition returns to its normal state. Usually, positive feedback systems reinforce conditions that do not happen very often, and negative feedback systems regulate conditions in the body that remain fairly stable over long periods. Figure (3): childbirth positive feedback loop Factors involved in homeostasis: 1. Maintenance of pH 2. Regulation of temperature 3. Maintenance of water balance 4. Maintenance of electrolyte balance 5. Supply of nutrients, oxygen, enzymes and hormones 6. Removal of metabolic and other waste products Page 4 of 9 Body Fluids compartments The cells of the human body live in a carefully regulated fluid environment. The fluid inside the cells, the intracellular fluid (ICF), occupies what is called the intracellular compartment, and the fluid outside the cells, the extracellular fluid (ECF), occupies the extracellular compartment. The barriers that separate these two compartments are the cell membranes. For life to be sustained, the body must rigorously maintain the volume and composition of the intracellular and extracellular compartments. To a large extent, such regulation is the result of transport across the cell membrane. The intracellular and extracellular fluids Total body water is the sum of the intracellular and extracellular fluid volumes. In a normal young adult male, it is about 60% of total body weight and in a young adult human female, it is about 50% of total body weight. Total body water accounts for a lower percentage of weight in females because they typically have more adipose tissue, and fat cells have a lower water content than muscle does. In thin persons, water content is more than in obese persons. In old age, water content is decreased due to increase in adipose tissue. The total quantity of body water in an average human being weighting about 70 kg is about 40 liters (60%). It is distributed into two major compartments namely: 1) - Intracellular fluid (ICF) forming 55% of total body water (22 liters) 2) - Extracellular fluid (ECF) forming 45% of the total body water (18 liters). Extracellular fluid is divided into: Intravascular fluid (inside the blood vessels). It is the blood plasma (3 L) Interstitial fluid (between cells) in the tissue spaces (12 L) Transcellular fluid: that includes cerebrospinal fluid, intraocular fluid, intraplerual fluid, peritoneal fluid, pericardial fluid (200-500ml) Others: as fluid in bones and joints and dense connective tissue. The “internal environment” is the ECF in which the cells live. The ECF that fills the narrow spaces between cells of tissues is known as interstitial fluid. ECF contains substances necessary for the survival of the cells. Hence, it is termed as “internal environment”. ECF serves as a transition between the external environment and ICF inside the cells. Therefore, homeostasis is maintaining a constant ECF compartment. External environment ECF ICF (cells) Figure (4): Body fluid movement between compartments. Body Fluids composition There are important differences in the solute composition of the various compartments of body fluid, and these have major implication for normal cell metabolism and function. The main distinction between ICF and ECF is that the dominant cation in ECF is Na+ while in ICF is K+. Cl- and HCO3- make up most of the balancing anions in ECF, while in ICF the principal negative charges are carried by phosphates and proteins (Table 1). There is normally zero net flux of water across the cell membrane, i.e ECF and ICF are in the osmotic equilibrium. Page 5 of 9 Another important distinction between the composition of plasma and interstitial fluid is that the plasma, but not the interstitial fluid, contains a substantial concentration of proteins. The mechanism for maintain this protein difference is the presence of a permeability barrier at the capillary wall which largely prevents the movement of capillaries under normal circumstances. The significance of this protein concentration gradient is that it makes an important contribution to the balance of forces across the capillary wall (colloid osmotic pressure of plasma). Na+ is the dominant cation in ECF, together with its accompanying anions account for 95% of the solutes present in this fluid compartment. Thus Na+ is responsible for nearly all of osmotic activity in ECF. So factors which deplete Na+ (hyponatremia) will be associated with a low ECF volume (hypovolemia), whereas Na+ retention (hypernatremia) is associated with expansion of ECF volume (hypervolemia). Osmosis and tonicity: The movement of water across a membrane in response to a solute concentration gradient is called osmosis. In osmosis water moves to dilute the more concentrated solution. Once concentrations are equal, movement of water stops. The concentration of solutes in a fluid creates the osmotic pressure of the solution, which in turn determines the movement of water through membranes Osmotic pressure: it is the mechanical pressure needed in the concentrated solution to prevent water movement from the diluted side. The movement of water can be prevented by applying some pressure in the solution with high solute concentration. This pressure is exerted by the solutes dissolved by water. The osmotic pressure in solutions is determined by osmolality. Normally, the osmotic pressure of the cytosol is the same as the osmotic pressure of the interstitial fluid outside cells. Osmolality: is the concentration of osmotically active substances in the solution. It is the number of Page 6 of 9 particles (osmoles) per kilogram of water. Osmolality describes the total concentration of all particles that are free in a solution. Thus, glucose contributes one particle, whereas fully dissociated NaCl contributes two. Particles bound to macromolecules do not contribute at all to osmolality. Osmolarity: is another term to express the osmotic concentration. It is the number of particles (osmoles) per liter of solution. The osmolarity of plasma = 290 mosm/L. Comparing osmolarities of two solutions: You can compare the osmolarities of 2 solutions as long as the concentrations are expressed in the same units: If the 2 solutions contain the same number of solute particles per unit volume, we say that the solutions are isosmotic If solution (A) has higher osmolarity than solution (B), we say that solution (A) is hyperosmotic and solution (B) is hypoosmotic Tonicity: Tonicity is a physiological term used to describe a solution and how such solution affects the cell volume if the cell were placed in the solution and allowed to come to equilibrium. Tonicity compares a solution and a cell. (table 2, figure 5 ) Table 2: the effect of tonicity on cell volume Table 2: the effect of tonicity on cell volume Page 7 of 9 Figure 5: The effect of different tonicities on the cell size Membrane potential: A particular characteristic of all living cells is that there is always an electrical potential difference between the outer and inner surface of its surrounding membrane. It is caused by unequal distribution of electrically charged ions on both sides of the membrane with prevalence of cations at the outer surface and anions at the inner surface. Factors involved in production of membrane potential: 1)- Selective permeability across the cell membrane: The chief ions on the outer surface of the membrane are: Na+, Cl-, HCO3-, with small amounts of K+. The chief ions on the inner surface are: K+, and proteins , with little amounts of Na+, Cl- and HCO3-. Under resting conditions, the permeability of cell membrane to various ions is a matter of selection. It contains leak channels which allow certain ions to pass and prevents others. Every channel is specifically selective for the passage of one or more ions. The selective permeability of the membrane will be as follow: impermeable to proteins, which create negative charge at the inner surface of the membrane semipermeable to Na+ and K+ ions: ü sodium channels are specifically selective for passage of Na+ ions (leak channels). Na+ ions try to pass from EC to IC space due to concentration gradient ü K+ ions are smaller than Na+ ions , therefore they can pass easily through K+ leak channels. Membrane permeability is 50-100 times more than its permeability to Na+ ions.K+ ions try to pass from IC to EC space. Freely permeable to Cl- and HCO3, which diffuse from outside to inside of the membrane according to their concentration gradient. Migration of ions cannot continue because once the state of equilibrium is reached, the membrane becomes polarized i.e with positive charge at the outer surface of the membrane and negative charge at the inner surface. The +ve charge on the outer surface repels the outflux of K+ ions The –ve charge on the inner surface prevents further passage of Cl- and HCO3 Any amount of Na+ leaked to interior of the cell is out fluxed by Na+ pump 2)- Sodium- potassium pump: The cell maintains a relatively high K+ concentration and low Na+ concentration, not by making its membrane totally impermeable to these ions but by using the Na-K pump to actively extrude Na+ from the cell and to actively transport K+ into the cell. It is the most important active transport mechanism in the body. (Figure 6) Na+- K+ pump is responsible for the distribution of Na+ and K+ ions across the cell membrane and the development of –ve electrical potential inside the cell. Page 8 of 9 Figure(6) : Na+-K+ pump Page 9 of 9